Patricia Hibberd, MD, PhD is a clinical investigator dedicated to patient-oriented research. Of the 23 trainees partially or completely mentored during the first four years of her K24 award, 12 (52%) now have their own NIH grants, a vastly accelerated pace compared to her K24 award period. The overarching goal of her K24 Mid- Career Investigator Award in Patient-Oriented Research renewal grant is to advance probiotic science through high quality translational clinical research, novel collaborations to optimize the potential impact of probiotics on the prevention and treatment of infectious diseases, and innovative scientific solutions to the challenges of regulation of probiotics as bio-therapeutics. The renewal grant objectives are to continue to mentor students, post-doctoral fellows, and junior faculty who will conduct patient-oriented translational research to expand knowledge about host-microbe and microbe-microbe interactions, and to develop new avenues for clinical applications of probiotics. Her mentoring program will leverage the research and teaching infrastructure of the Harvard Catalyst/CTSA, as well as her two funded U01 grants and expertise of her multidisciplinary collaborators dedicated to the study of probiotics. Goals for the mentees are to obtain formal training in clinical/ translational research methodology, ethics, and regulatory science, to conduct mentored pilot studies and to develop grant applications for patient-oriented research. She will also provide longer-term career support through research check-ups to sustain the pool of well-trained clinical researchers as they embark on independent academic careers in meritorious CAM research. The new research direction in this renewal grant will greatly expand the goals of U01AT002952 to investigate the early response to influenza immunization (inactivated and live attenuated) in the elderly in subjects receiving probiotics as an immune adjuvant vs. placebo, by studying urinary protein profiles using mass spectrophotometry, with Harvard CTSA collaborators. Early vaccine responses 24, 48 and 72 hours after immunization, in the presence vs. absence of the probiotic immune adjuvant will be compared using proteomics. These data will greatly complement the U01 funded assessment of vaccine immune response that includes influenza titers (HAI and MN), systemic and mucosal IgA titers, and novel biomarkers such as the richness and diversity of gastrointestinal and respiratory microbiota and mRNA expression of pro and inflammatory genes and different signaling pathways 3, 4 and 8 weeks after influenza vaccine immunization. Proteomic profiles in vaccine responders vs. non-responders may improve understanding of individual differences in response of the elderly to immunization.